Level 1 of 6Core
Febrile neutropenia and neutropenic sepsis
The core to-do list — diagnose and manage, at a glance
Diagnose— recognise it
- The definition: after cytotoxic chemotherapy, a single oral temperature ≥38.3°C, or ≥38°C sustained over one hour, with neutrophils below 0.5 × 10⁹/L (or below 1.0 if the nadir will fall below 0.5 within 48 hours). NICE adds the clause that catches the sickest: a neutropenic patient with any other signs of significant sepsis — the hypotensive, rigoring, confused or hypothermic patient with no recorded fever satisfies the definition and carries a HIGHER mortality.
- The safest operating rule: treat fever, or unexplained deterioration, in any patient within about six weeks of chemotherapy as febrile neutropenia until the differential count says otherwise. It is the neutrophil count that matters, not the white cell count — in acute leukaemia a WCC as high as 300 × 10⁹/L commonly conceals profound neutropenia with blasts predominating.
- The classical signs of infection are made of neutrophils: pneumonia may give a near-normal chest radiograph, an abscess no pus, peritonitis little guarding, urinary infection no pyuria — a normal examination does not lower the probability of serious infection. Fever is often the only feature; in perhaps half of episodes no source is ever identified.
- Danger signs of septic shock: systolic BP below 90 mmHg or a fall of over 40 mmHg; heart rate above 120/min; respiratory rate above 24/min; new oxygen requirement; new confusion; lactate above 2 mmol/L (above 4 predicts high mortality); urine below 0.5 mL/kg/h; hypothermia below 36°C (a worse sign than fever); profound neutropenia below 0.1 × 10⁹/L.Not available at your setup — Arterial blood gas.
- Examine where infection hides: mouth and pharynx (mucositis, thrush, herpetic crusting), skin including the back, every catheter exit site and tunnel, the perineum and perianal region (inspect with a light — no digital rectal examination), chest and abdomen. Rigors reproducibly a few minutes after a central line flush point to catheter infection; right iliac fossa pain with diarrhoea and distension is neutropenic enterocolitis until excluded.
- Age and drugs blunt the picture: the elderly present with delirium, falls or being off legs, often without fever; patients on corticosteroids may not mount a fever at all; beta-blockade masks tachycardia. Children compensate then decompensate abruptly — hypotension in a child is pre-terminal: act on tachycardia, rising respiratory rate, prolonged capillary refill, drowsiness and a parent reporting the child is not themselves.
Manage now— do this, in order
- High-dose broad-spectrum IV antibiotics ideally within one hour of admission, without awaiting test results — the blood count confirms the diagnosis, it does not license the delay; time to effective antibiotic is the most modifiable determinant of survival.Doctor / Nurse
- Cultures first — but first means within minutes: two peripheral blood culture sets plus one from every lumen of any central catheter, urine, stool if diarrhoea, swabs of line site and wounds, sputum, respiratory viral PCR.Not available at your setup — Blood culture.
- Standard first-line monotherapy: piperacillin–tazobactam 4.5 g IV every 6–8 hours (paediatric 90 mg/kg every 6–8 hours, max 4.5 g/dose). Cover must include *Pseudomonas* and Gram-negative bacilli — never ceftriaxone or any agent without antipseudomonal cover as sole empirical therapy; follow local resistance patterns.Doctor / Nurse
- Meropenem 1 g IV every 8 hours (paediatric 20 mg/kg, max 1 g/dose) if shocked, recently exposed to piperacillin–tazobactam, or known ESBL colonisation; alternatives cefepime or ceftazidime 2 g IV every 8 hours (paediatric 50 mg/kg, max 2 g/dose). Severe penicillin allergy (anaphylaxis): aztreonam 2 g IV every 8 hours or ciprofloxacin 400 mg IV every 8–12 hours plus a glycopeptide — but a rash alone should not deprive a shocked patient of a beta-lactam.Doctor / Nurse
- Add gentamicin 5–7 mg/kg IV once daily (ideal body weight; paediatric 7 mg/kg) or amikacin 15 mg/kg only for the shocked patient or local resistance. Add vancomycin 15–20 mg/kg IV every 8–12 hours (load 25–30 mg/kg if severe; paediatric 15 mg/kg every 6 hours) or teicoplanin only for a specific reason — infected line site, MRSA colonisation, severe mucositis, skin source or instability — and stop at 48–72 hours if no Gram-positive isolate emerges.Doctor / Nurse
- Resuscitate in parallel: oxygen to 94–98% (88–92% if hypercapnic risk); crystalloid 500 mL over 15 minutes in an unstable adult (250 mL if frail or cardiac; 10–20 mL/kg in a child); noradrenaline first choice if hypotension persists after 20–30 mL/kg; target urine ≥0.5 mL/kg/h adult, ≥1 mL/kg/h child. Paracetamol 1 g up to four times daily (children 15 mg/kg/dose, max 60 mg/kg/24 h) — avoid NSAIDs and aspirin.Doctor / Nurse
- Never perform a digital rectal examination, take a rectal temperature or give a suppository; avoid IM injections in the thrombocytopenic patient; no anti-motility agents for diarrhoea until *Clostridioides difficile* and typhlitis are excluded — instrumenting a mucosa that cannot defend itself seeds bacteraemia.
- Reassess at 48–96 hours: improving and afebrile — continue and narrow if a pathogen is isolated; febrile but stable — do not change antibiotics reflexively: re-examine head to toe, re-culture every lumen, review for drug fever, image. Febrile and unstable — broaden to meropenem 1 g every 8 hours with an additional Gram-negative agent (ciprofloxacin or tobramycin) if critically ill.Doctor / Nurse
- Think fungus at day 3–5, not day 1: if fever has not resolved after 3–5 days with CT or sensitive blood-test evidence of disseminated fungal infection, add liposomal amphotericin B, voriconazole or caspofungin — treat confirmed or suspected systemic *Candida* or *Aspergillus* for up to three weeks, and in systemic candidaemia the intravenous catheter must be removed.Doctor / Nurse
| Drug (IV) | Adult | Paediatric |
|---|---|---|
| Piperacillin–tazobactam | 4.5 g q6–8h | 90 mg/kg q6–8h (max 4.5 g) |
| Meropenem | 1 g q8h | 20 mg/kg q8h (max 1 g) |
| Cefepime / ceftazidime | 2 g q8h | 50 mg/kg q8h (max 2 g) |
| Gentamicin | 5–7 mg/kg od (IBW) | 7 mg/kg od |
| Vancomycin | 15–20 mg/kg q8–12h (load 25–30 if severe) | 15 mg/kg q6h |
| Aztreonam (severe allergy) | 2 g q8h | 30 mg/kg q6–8h |
Refer / escalate
Escalate to critical care immediately for systolic BP below 90 mmHg or a fall of over 40 mmHg, heart rate above 120/min, respiratory rate above 24/min, a new oxygen requirement, new confusion, lactate above 2 mmol/L, urine below 0.5 mL/kg/h, hypothermia below 36°C, or hypotension persisting after 20–30 mL/kg of fluid — and discuss every episode with the treating oncology or haematology team the same day.
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